title: Virus-associated hemophagocytic syndrome as a major contributor to death in patients with 2009 influenza A (H1N1) infection.
abstract: BACKGROUND
  Virus-associated hemophagocytic syndrome (VAHS) is a severe complication of various viral infections often resulting in multiorgan failure and death. The purpose of this study was to describe baseline characteristics, development of VAHS, related treatments and associated mortality rate of consecutive critically ill patients with confirmed 2009 influenza A (H1N1) infection and respiratory failure.
  
  
  METHODS
  We conducted a prospective observational study of 25 critically ill patients with 2009 influenza A (H1N1) infection at a single-center intensive care unit in Germany between 5 October 2009 and 4 January 2010. Demographic data, comorbidities, diagnosis of VAHS, illness progression, treatments and survival data were collected. The primary outcome measure was the development of VAHS and related mortality. Secondary outcome variables included duration of mechanical ventilation, support of extracorporeal membrane oxygenation and duration of viral shedding.
  
  
  RESULTS
  VAHS developed in 9 (36%) of 25 critically ill patients with confirmed 2009 influenza A (H1N1) infection, and 8 (89%) of them died. In contrast, the mortality rate in the remaining 16 patients without VAHS was 25% (P = 0.004 for the survival difference in patients with or without VAHS by log-rank analysis). The patients were relatively young (median age, 45 years; interquartile range (IQR), 35 to 56 years of age); however, 18 patients (72%) presented with one or more risk factors for a severe course of illness. All 25 patients received mechanical ventilation for severe acute respiratory distress syndrome and refractory hypoxemia, with a median duration of mechanical ventilation of 19 days (IQR, 13 to 26 days). An additional 17 patients (68%) required extracorporeal membrane oxygenation for a median of 10 days (IQR, 6 to 19 days).
  
  
  CONCLUSIONS
  The findings of this study raise the possibility that VAHS may be a frequent complication of severe 2009 influenza A (H1N1) infection and represents an important contributor to multiorgan failure and death.
authors.affiliation: Departments of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany. Beutel.Gernot@mh-hannover.de
authors.forename: Gernot
authors.initials: G
authors.lastname: Beutel
authors.forename: Olaf
authors.initials: O
authors.lastname: Wiesner
authors.forename: Matthias
authors.initials: M
authors.lastname: Eder
authors.forename: Carsten
authors.initials: C
authors.lastname: Hafer
authors.forename: Andrea S
authors.initials: AS
authors.lastname: Schneider
authors.forename: Jan T
authors.initials: JT
authors.lastname: Kielstein
authors.forename: Christian
authors.initials: C
authors.lastname: Kühn
authors.forename: Albert
authors.initials: A
authors.lastname: Heim
authors.forename: Tina
authors.initials: T
authors.lastname: Ganzenmüller
authors.forename: Hans-Heinrich
authors.initials: HH
authors.lastname: Kreipe
authors.forename: Axel
authors.initials: A
authors.lastname: Haverich
authors.forename: Andreas
authors.initials: A
authors.lastname: Tecklenburg
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.forename: Tobias
authors.initials: T
authors.lastname: Welte
authors.forename: Marius M
authors.initials: MM
authors.lastname: Hoeper
mesh_terms: D000328:Adult; D016638:Critical Illness; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype; D007251:Influenza, Human / Q000401:mortality*; D051359:Lymphohistiocytosis, Hemophagocytic / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index